Mast Cells and Mas-related G Protein-coupled Receptor X2: Itching for Novel Pathophysiological Insights to Clinical Relevance

Voehringer D. Protective and pathological roles of mast cells and basophils. Nat Rev Immunol. 2013;13:362–75.

Article  PubMed  CAS  Google Scholar 

Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, et al. Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich’s visions to precision medicine concepts. Theranostics. 2020;10:10743–68.

Article  PubMed  PubMed Central  CAS  Google Scholar 

McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519:237–41.

Article  PubMed  CAS  Google Scholar 

Deepak V, Komarow HD, Alblaihess AA, Carter MC, Metcalfe DD, Ali H. Expression of MRGPRX2 in skin mast cells of patients with maculopapular cutaneous mastocytosis. J Allergy Clin Immunol Pract. 2021;9:3841-3.e1.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fujisawa D, Kashiwakura J, Kita H, Kikukawa Y, Fujitani Y, Sasaki-Sakamoto T, et al. Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. J Allergy Clin Immunol. 2014;134:622-33.e9.

Article  PubMed  CAS  Google Scholar 

Kawakami T, Kasakura K. Mast Cell Eavesdropping on Bacterial Communications. Cell Host Microbe. 2019;26:3–5.

Article  PubMed  CAS  Google Scholar 

Subramanian H, Gupta K, Ali H. Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 2016;138:700–10.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Meixiong J, Anderson M, Limjunyawong N, Sabbagh MF, Hu E, Mack MR, et al. Activation of mast-cell-expressed Mas-related G protein-coupled receptors drives non-histaminergic Itch. Immunity. 2019;50:1163-71.e5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Giavina-Bianchi P, Gonçalves DG, Zanandréa A, Borges de Castro R, Garro LS, Kalil J, et al. Anaphylaxis to quinolones in mastocytosis: Hypothesis on the mechanism. J Allergy Clin Immunol In Practice. 2019;7:2089–90.

Article  Google Scholar 

Dong X, Han S, Zylka MJ, Simon MI, Anderson DJ. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell. 2001;106:619–32.

Article  PubMed  CAS  Google Scholar 

Liu Q, Tang Z, Surdenikova L, Kim S, Patel KN, Kim A, et al. Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell. 2009;139:1353–65.

Article  PubMed  PubMed Central  Google Scholar 

Paton WD. Compound 48/80: a potent histamine liberator. Br J Pharmacol Chemother. 1951;6:499–508.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kashem SW, Subramanian H, Collington SJ, Magotti P, Lambris JD, Ali H. G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: roles of Mas-related genes MrgX1 and MrgX2. Eur J Pharmacol. 2011;668:299–304.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Yang F, Guo L, Li Y, Wang G, Wang J, Zhang C, et al. Structure, function and pharmacology of human itch receptor complexes. Nature. 2021;600:164–9.

Article  PubMed  CAS  Google Scholar 

Cao C, Kang HJ, Singh I, Chen H, Zhang C, Ye W, et al. Structure, function and pharmacology of human itch GPCRs. Nature. 2021;600:170–5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wolf K, Kühn H, Boehm F, Gebhardt L, Glaudo M, Agelopoulos K, et al. A group of cationic amphiphilic drugs activates MRGPRX2 and induces scratching behavior in mice. J Allergy Clin Immunol. 2021;148:506-22.e8.

Article  PubMed  CAS  Google Scholar 

Reddy VB, Azimi E, Chu L, Lerner EA. Mas-related G-protein coupled receptors and cowhage-induced itch. J Invest Dermatol. 2018;138:461–4.

Article  PubMed  CAS  Google Scholar 

Hamamura-Yasuno E, Matsushita J, Sato S, Shimada T, Tsuchiya Y, Fujimoto K, et al. Determination of key residues in MRGPRX2 to enhance pseudo-allergic reactions induced by fluoroquinolones. Sci Rep. 2022;12:6650.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chaki S, Alkanfari I, Roy S, Amponnawarat A, Hui Y, Oskeritzian CA, et al. Inhibition of Orai channel function regulates Mas-related G protein-coupled receptor-mediated responses in mast cells. Front Immunol. 2021;12:803335.

Article  PubMed  CAS  Google Scholar 

Bawazir M, Amponnawarat A, Hui Y, Oskeritzian CA, Ali H. Inhibition of MRGPRX2 but not FcεRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist. Front Immunol. 2022;13:1033794.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Yang F, Limjunyawong N, Peng Q, Schroeder JT, Saini S, MacGlashan D Jr, et al. Biological screening of a unique drug library targeting MRGPRX2. Front Immunol. 2022;13:997389.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Azimi E, Reddy VB, Lerner EA. Brief communication: MRGPRX2, atopic dermatitis and red man syndrome. Itch (Phila). 2017;2:e5.

PubMed  Google Scholar 

Lembo PM, Grazzini E, Groblewski T, O’Donnell D, Roy MO, Zhang J, et al. Proenkephalin A gene products activate a new family of sensory neuron–specific GPCRs. Nat Neurosci. 2002;5:201–9.

Article  PubMed  CAS  Google Scholar 

Kiatsurayanon C, Niyonsaba F, Chieosilapatham P, Okumura K, Ikeda S, Ogawa H. Angiogenic peptide [AG]-30/5C activates human keratinocytes to produce cytokines/chemokines and to migrate and proliferate via MrgX receptors. J Dermatol Sci. 2016;83:190–9.

Article  PubMed  CAS  Google Scholar 

Porebski G, Kwiecien K, Pawica M, Kwitniewski M. Mas-related G protein-coupled receptor-X2 (MRGPRX2) in drug hypersensitivity reactions. Front Immunol. 2018;9:3027.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13:397–406.

Article  PubMed  CAS  Google Scholar 

Babina M, Wang Z, Roy S, Guhl S, Franke K, Artuc M, et al. MRGPRX2 is the codeine receptor of human skin mast cells: desensitization through β-Arrestin and lack of correlation with the FcεRI pathway. J Invest Dermatol. 2021;141:1286-96.e4.

Article  PubMed  CAS  Google Scholar 

Shtessel M, Limjunyawong N, Oliver ET, Chichester K, Gao L, Dong X, et al. MRGPRX2 activation causes increased skin reactivity in patients with chronic spontaneous urticaria. J Invest Dermatol. 2021;141:678-81.e2.

Article  PubMed  CAS  Google Scholar 

Trier AM, Kim BS. Structural insights into MRGPRX2: A new vision of itch and allergy. J Allergy Clin Immunol. 2022;149:1221–2.

Article  PubMed  CAS  Google Scholar 

Chompunud Na Ayudhya C, Ali H. Mas-related G protein-coupled receptor-X2 and its role in non-immunoglobulin E-mediated drug hypersensitivity. Immunol Allergy Clin North Am. 2022;42:269–84.

Comments (0)

No login
gif